The interplay between vaginal and gut microbiota and their collective impact on live birth outcomes remains poorly characterized. This study investigated the association between vaginal and gut microbiota and live birth outcomes in women undergoing frozen-thawed embryo transfer (FET). Vaginal and fecal samples were collected from 137 infertile women (64 controls, 73 with polycystic ovary syndrome (PCOS) undergoing FET and analyzed by 16S rRNA gene sequencing. Machine learning models based on genus-level abundance were used to predict live birth outcomes, and PICRUSt2 was employed to infer functional profiles of microbial communities. Significant differences in microbial composition, β-diversity, and functional profiles were observed between live birth (LB) and non-live birth (NLB) groups (all p < 0.05). NLB cases exhibited synchronized dysbiosis across both niches, with opposing patterns between subgroups: control-NLB showed increased β-diversity, whereas PCOS-NLB showed reduced β-diversity in both vaginal and gut microbiota. Notably, the combined signature of vaginal and gut taxa outperformed single-niche biomarkers for predicting live birth outcomes. In controls, vaginal Ralstonia and gut Escherichia-Shigella achieved an AUC of 0.888. Strikingly, in PCOS patients, we identified a robust, disease-specific interaction: vaginal Streptococcus and gut Bacteroides not only showed high combined predictive performance (AUC = 0.905) but also exhibited a strong positive correlation (r = 0.782, p < 0.001), suggesting a PCOS-associated microbial interaction network. These findings reveal synchronized dysbiosis of vaginal and gut microbiota in NLB outcomes, with vaginal microbiota showing a more direct association with live birth. In PCOS, a specific vaginal Streptococcus-gut Bacteroides axis suggests a disease-specific microbial interaction network associated with reproductive failure in PCOS. Assessing both microbial ecosystems prior to FET may improve risk stratification and guide therapeutic interventions targeting the vaginal-gut axis.

QseC is a sensor component of the two-component system (TCS) QseBC in Glaesserella parasuis (G. parasuis). Quantitative proteomics identifies 39 differentially expressed proteins (DEPs) (12 upregulated, 27 downregulated) in ΔqseC, with the lipid metabolism enzyme PlsB emerging as a core hub showing concurrent upregulation in total protein expression and phosphorylation. Phosphoproteomics detects 95 phosphorylation sites, demonstrating predominant serine phosphorylation (40%) and significant PlsB/SerS hyperphosphorylation. Functional analyses show that deleting the qseC gene disrupts cellular balance. This change causes an energy crisis involving ATPase imbalance and carbohydrate metabolism defects. It also weakens the cell membrane by reducing key lipopolysaccharide (LPS) biosynthesis proteins like LpxB, KdsB, and WaaQ. Additionally, iron uptake becomes impaired because genes such as hemG and fbpC2 are suppressed, along with defense proteins HsdR and ApxIB. Finally, cells adopt an "offensive-defensive shift" survival strategy. They do this by reducing energy-intensive defenses like UvrA-mediated DNA repair and β-lactam resistance, while increasing lipid storage (PlsB) and RNA degradation. Protein-protein interaction (PPI) networks confirm 10 core proteins that collectively maintain proteostasis and stress adaptation, with PlsB serving as the central coordinator of membrane synthesis and environmental adaptation.

IntroductionGlaesserella parasuis (G. parasuis) causes agent Glässer’s disease in swine. This study investigated the mechanism of QseC in G. parasuis.MethodsThe study utilized transcriptomic and metabolomic sequencing techniques. The ΔqseC mutant was examined using transmission electron microscopy.ResultsTransmission electron microscopy revealed that ΔqseC mutant exhibited cell wall dissolution and cytoplasmic rarefaction, indicating membrane homeostasis disruption. Metabolomics analysis identified 819 metabolites, with 24/36 showing significant alterations in positive/negative ion modes. KEGG enrichment indicated abnormalities in amino acid synthesis and quorum sensing. Transcriptomic revealed 663 differentially expressed genes (DEGs), including upregulated membrane synthesis genes (plsB and wecA) and downregulated virulence factors (hrpA and pilW). Integrated analysis demonstrated that plsB and wecA formed association networks with methionine and prostaglandin metabolites.DiscussionThese results establish QseC’s global regulatory role in G. parasuis, providing insights for novel control strategies.

IntroductionIn recent years, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease globally. Studies indicate that the gut-liver axis plays an important role in the occurrence and development of this disease. Our previous studies showed that the gut microbiota and gut metabolites in mice with NAFLD changed significantly. However, it is unclear whether these changes influenced the disease process through serum metabolites.MethodsWe conducted a non-targeted metabolome analysis on serum metabolites and systematically investigated the correlations between serum metabolites, gut microbiota, gut metabolites, and phenotypic index. Additionally, we traced the potential origins of serum metabolites and analyzed host-microbial interactions to elucidate the underlying mechanisms linking changes in serum metabolites with gut microbiota and gut metabolites.ResultsThe findings suggest that the imbalance of gut pathogenic microbiota, specifically Blautia and Helicobacter, and beneficial microbiota such as Allobaculum, in mice with nonalcoholic fatty liver disease may be an important cause of gut metabolic disorders. This disorder results in a reduction of unsaturated fatty acid content, particularly a decrease in Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA), and an accumulation of branched fatty acids in the serum. Consequently, there is a significant elevation in liver injury indices, potentially exacerbating the progression of nonalcoholic fatty liver disease and obesity in mice.DiscussionThese results suggest that serum metabolites are influenced by gut microbiota and their metabolites. The variations in serum metabolites provide valuable insights into the relationship between gut microbiota and their metabolites in the context of nonalcoholic fatty liver disease.

NASH cirrhosis is a late-stage nonalcoholic fatty liver disease (NAFLD) characterized by high morbidity, high relapse rate, and high mortality, which is clinical to treat. Presently, liver transplantation is the most effective radical treatment, but it is difficult to be widely carried out due to the problems of large surgical trauma, lack of liver donors, and strong immunological rejection. Bone marrow mesenchymal stem cells (BMSCs) are a type of stem cell with characteristics of self-replication, multidirectional differentiation, and easy accessibility. The use of BMSCs for cell transplantation therapy has the advantages of fewer complications and significant efficacy, and it has become an important option for cell transplantation therapy, especially for liver diseases. In this paper, we will review the studies related to the use of BMSCs for the treatment of NASH cirrhosis in recent years.

The qseC gene is a two-component system that encodes a histidine protein kinase and is highly conserved among different Glaesserella parasuis strains. In this study, we used qRT-PCR and enzyme-linked immunosorbent assay to confirm that Toll-like receptor 4 (TLR4) plays a role in the expression of proinflammatory cytokines interleukin (IL)-1 beta and IL-6 by stimulating RAW 264.7 macrophages with QseC. Furthermore, we revealed that blocking the p38 and NF-kappa B pathways that regulate signaling can significantly reduce the production of proinflammatory cytokines induced by QseC. In summary, our data suggest that QseC is a novel proinflammatory mediator that induces TLR4-dependent proinflammatory activity in RAW 264.7 macrophages through the p38 and NF-kappa B pathways.

Matcha shows promise for diabetes, obesity, and gut microbiota disorders. Studies suggest a significant link between gut microbiota, metabolites, and obesity. Thus, matcha may have a positive impact on obesity by modulating gut microbiota and metabolites. This study used 16S rDNA sequencing and untargeted metabolomics to examine the cecal contents in mice. By correlation analysis, we explored the potential mechanisms responsible for the positive effects of matcha on obesity. The results indicated that matcha had a mitigating effect on the detrimental impacts of a high-fat diet (HFD) on multiple physiological indicators in mice, including body weight, adipose tissue weight, serum total cholesterol (TC), and low-density lipoprotein (LDL) levels, as well as glucose tolerance. Moreover, it was observed that matcha had an impact on the structural composition of gut microbiota and gut metabolites. Specifically, matcha was able to reverse the alterations in the abundance of certain obesity-improving bacteria, such as Alloprevotella, Ileibacterium, and Rikenella, as well as the abundance of obesity-promoting bacteria Romboutsia, induced by a HFD. Furthermore, matcha can influence the levels of metabolites, including formononetin, glutamic acid, pyroglutamic acid, and taurochenodeoxycholate, within the gastrointestinal tract. Additionally, matcha enhances caffeine metabolism and the HIF-1 signaling pathway in the KEGG pathway. The results of the correlation analysis suggest that formononetin, theobromine, 1,3,7-trimethyluric acid, and Vitamin C displayed negative correlation with both the obesity phenotype and microbiota known to exacerbate obesity, while demonstrating positive correlations with microbiota that alleviated obesity. However, glutamic acid, pyroglutamic acid, and taurochenodeoxycholate had the opposite effect. In conclusion, the impact of matcha on gut metabolites may be attributed to its modulation of the abundance of Alloprevotella, Ileibacterium, Rikenella, and Romboutsia within the gastrointestinal tract, thereby potentially contributing to the amelioration of obesity.

Obesity is a multifaceted health concern that is impacted by genetic, environmental, and behavioral factors, with varying levels of individual susceptibility. Research has identified distinct physiological characteristics among individuals with differing susceptibilities to obesity. Prior research has demonstrated notable variances in gut microbiota and gut metabolites between obesity-prone (OP) individuals and those obesity-resistance (OR). However, the potential impact of these differences on serum metabolites remains uncertain, as does the potential role of serum metabolite changes in influencing susceptibility to obesity. We performed non-targeted metabolomic analysis on serum samples from OP and OR mice. Subsequently, correlation analysis was conducted on the data pertaining to serum metabolites, gut microbiota, gut metabolites, obesity-related physiological indicators, among other factors. This study aimed to investigate the association between alterations in serum metabolites and gut microbiota and metabolites in OP and OR mice, as well as to examine the impact of serum metabolites on susceptibility to obesity. Our research demonstrates that following HFD, gut 8Z,11Z,14Z-Eicosatrienoic acid (ESA) and gut Eicosapentaenoic acid (EPA) can impact lipid levels through the regulation of serum Arachidonic acid (AA) and serum EPA. EPA also influences the abundance of Lachnospiraceae_NK4A136_group, resulting in increased lipid accumulation. Moreover, Ruminiclostridium_9 exacerbates levels of serum saturated fatty acids and serum AA by decreasing EPA. Additionally, gut Hydroxybenzoic acid influences susceptibility to lipid accumulation by elevating serum Choline levels. These alterations contribute to the development of susceptibility to obesity, indicating that variations in serum metabolites play a significant role in susceptibility disparities, with the serum metabolites being influenced by gut microbiota and gut metabolites.

As a multi-factorial disease, obesity has become one of the major health problems in the world, and it is still increasing rapidly. Konjac supplementation, as a convenient dietary therapy, has been shown to be able to regulate gut microbiota and improve obesity. However, the specific mechanism by which konjac improves obesity through gut microbiota remains to be studied. In this study, a high-fat diet (HFD) was used to induce a mouse obesity model, and 16S rDNA sequencing and an untargeted metabolomics were used to investigate the impact of konjac on gut microbiota and gut metabolites in HFD-induced obese mice. The results show that konjac can reduce the body weight, adipose tissue weight, and lipid level of high-fat diet induced obese mice by changing the gut microbiota structure and gut metabolic profile. Association analysis revealed that konjac supplementation induced changes in gut microbiota, resulting in the up-regulation of 7-dehydrocholesterol and trehalose 6-phosphate, as well as the down-regulation of glycocholic acid and ursocholic acid within the Secondary bile acid biosynthesis pathway, ultimately leading to improvements in obesity. Among them, g_Acinetobacter (Greengene ID: 911888) can promote the synthesis of 7-dehydrocholesterol by synthesizing ERG3. g_Allobaculum (Greengene ID: 271516) and g_Allobaculum (Greengene ID: 259370) can promote the breakdown of trehalose 6-phosphate by synthesizing glvA. Additionally, the down-regulation of glycocholic acid and ursocholic acid may be influenced by the up-regulation of Lachnospiraceae_NK4A136_group. In conclusion, konjac exerts an influence on gut metabolites through the regulation of gut microbiota, thereby playing a pivotal role in alleviating obesity induced by a high-fat diet.

Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.

The senescence of mesenchymal stem cells (MSCs) is closely related to aging and degenerative diseases. Curcumin exhibits antioxidant and anti-inflammatory effects and has been extensively used in anti-cancer and anti-aging applications. Studies have shown that curcumin can promote osteogenic differentiation, autophagy and proliferation of MSCs. Liposome, as a nano-carrier, provides a feasible strategy for improving the bioavailability and controlled-release profile of curcumin.This study aimed to evaluate the effects of curcumin liposomes (Cur-Lip) on the senescence of rat bone marrow mesenchymal stem cells (rBMSCs). Based on network pharmacology, we predicted the targets and mechanisms of curcumin on senescence of MSC. 23 key targets of Cur were associated with MSC senescence were screened out and mitophagy signaling was significantly enriched. Cur-Lip treatment alleviated senescence of D-galactose (D-gal)-induced rBMSCs, protected mitochondrial function, and activated mitophagy, which may be related to mitochondrial fission. Inhibition of mitophagy attenuated the protective effects of Cur-lip on mitochondrial function and senescence of rBMSCs. Our findings suggested that Cur-Lip could alleviate senescence of rBMSC and improve mitochondrial function by activating mitophagy.

IntroductionIt is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain.MethodsIn this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites.ResultsAfter a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.

Globally, ~8%−12% of couples confront infertility issues, male-related issues being accountable for 50%. This review focuses on the influence of gut microbiota and their metabolites on the male reproductive system from five perspectives: sperm quality, testicular structure, sex hormones, sexual behavior, and probiotic supplementation. To improve sperm quality, gut microbiota can secrete metabolites by themselves or regulate host metabolites. Endotoxemia is a key factor in testicular structure damage that causes orchitis and disrupts the blood-testis barrier (BTB). In addition, the gut microbiota can regulate sex hormone levels by participating in the synthesis of sex hormone-related enzymes directly and participating in the enterohepatic circulation of sex hormones, and affect the hypothalamic-pituitary-testis (HPT) axis. They can also activate areas of the brain that control sexual arousal and behavior through metabolites. Probiotic supplementation can improve male reproductive function. Therefore, the gut microbiota may affect male reproductive function and behavior; however, further research is needed to better understand the mechanisms underlying microbiota-mediated male infertility.

QseC is a membrane sensor kinase that enables bacteria to perceive autoinducers -3, adrenaline, and norepinephrine to initiate downstream gene transcription. In this study, we found that the QseC protein of Glaesserella parasuis can serve as an effective antigen to activate the host's immune response. Therefore, we investigated the immunogenicity and host protective effect of this protein. ELISA and indirect immunofluorescence results showed that QseC protein can induce high titer levels of humoral immunity in mice and regularly generate specific serum antibodies. We used MTS reagents to detect lymphocyte proliferation levels and found that QseC protein can cause splenic lymphocyte proliferation with memory and specificity. Further immunological analysis of the spleen cell supernatant revealed significant upregulation of levels of IL-1β, IL-4 and IFN-γ in the QseC+adjuvant group. In the mouse challenge experiment, it was found that QseC+adjuvant can provide effective protection. The results of this study demonstrate that QseC protein provides effective protection in a mouse model and has the potential to serve as a candidate antigen for a novel subunit vaccine for further research.

高校的核心内容是教学与科研工作,而高校实验动物管理对教学、科研工作的正常开展起着非常重要的作用.目前高校实验动物中心的建设发展迅速,如相应的管理和服务力度不够,将会影响和阻滞高校的教学和科研工作,更会带来巨大的生物安全隐患.近年来,为了提升管理服务效率,摆脱监管困境,西南医科大学结合自身运行特点,开始尝试研发信息化管理服务平台,探索科学高效的实验动物科研服务管理模式.文章从该平台的建设意义、系统功能、建设成效等方面进行简要介绍,为广大医学院校的实验动物管理工作提供参考.

The family Alloherpesviridae contains herpesviruses of fish and amphibians. Due to the significant economic losses to aquaculture that herpesviruses can cause, the primary areas of research interest are concerning their pathogenesis and prevention. Despite alloherpesvirus genomic sequences becoming more widely accessible, methods regarding their genus/species classification are still relatively unexplored. In the present study, the phylogenetic relationships between 40 completely sequenced alloherpesviruses were illustrated by the viral proteomic tree (ViPTree), which was divided into three monophyletic groups, namely Cyprinivirus, Ictalurivirus and Batrachovirus. Additionally, average nucleotide identity (ANI) and average amino acid identity (AAI) analyses were performed across all available sequences and clearly displayed species boundaries with the threshold value of ANI/AAI set at 90%. Subsequently, core-pan analysis uncovered 809 orthogroups and 11 core genes shared by all 40 alloherpesvirus genome sequences. For the former, a 15 percent identity depicts a clear genus boundary; for the latter, 8 of them may be qualified for phylogenetic analysis based on amino acid or nucleic acid sequences after being verified using maximum likelihood (ML) or neighbor-joining (NJ) phylogenetic trees. Finally, although the dot plot analysis was valid for the members within Ictalurivirus, it was unsuccessful for Cyprinivirus and Batrachovirus. Taken together, the comparison of individual methodologies provides a wide range of alternatives for alloherpesviruses classification under various circumstances.

Background: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. Objective: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. Methods: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified auto-phagy enhancers were evaluated in multiple C. elegans ND models by measuring A beta-, Tau-, alpha-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 x Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. Results: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited A beta, alpha-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 x Tg-AD mice. Conclusion: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy.

• 868 lncRNAs was differentially expressed in control and T. mentagrophytes -infected keratinocytes. • LncRNA–mRNA association analysis revealed the existence of 36 antisense, 128 cis -regulatory, and 458,338 trans -regulatory relationships. • Functional enrichment analyses showed that the differentially expressed lncRNAs were mainly related to adaptive and innate immune responses.

Introduction As a representation of the gut microbiota, fecal and cecal samples are most often used in human and animal studies, including in non-alcoholic fatty liver disease (NAFLD) research. However, due to the regional structure and function of intestinal microbiota, whether it is representative to use cecal or fecal contents to study intestinal microbiota in the study of NAFLD remains to be shown. Methods The NAFLD mouse model was established by high-fat diet induction, and the contents of the jejunum, ileum, cecum, and colon (formed fecal balls) were collected for 16S rRNA gene analysis. Results Compared with normal mice, the diversity and the relative abundance of major bacteria and functional genes of the ileum, cecum and colon were significantly changed, but not in the jejunum. In NAFLD mice, the variation characteristics of microbiota in the cecum and colon (feces) were similar. However, the variation characteristics of intestinal microbiota in the ileum and large intestine segments (cecum and colon) were quite different. Discussion Therefore, the study results of cecal and colonic (fecal) microbiota cannot completely represent the results of jejunal and ileal microbiota.

Background The immunomodulatory function of mesenchymal stem cells (MSCs) has been considered to be vital for MSC-based therapies. Many works have been devoted to excavate effective strategies for enhancing the immunomodulation effect of MSCs. Nonetheless, canine MSC-mediated immunomodulation is still poorly understood. Methods and results The inflammatory microenvironment was simulated through the employment of interferon-γ (IFN-γ) in a culture system. Compared with unstimulated cBMSCs, IFN-γ stimulation increased the mRNA levels of Toll-like receptor 3 ( TLR3 ) and indoleamine 2, 3-dioxygenase 1 ( IDO-1 ), and simultaneously enhanced the secretion of immunosuppressive molecules, including interleukin (IL)-10, hepatocyte growth factor (HGF), and kynurenine in cBMSCs. IFN-γ stimulation significantly enhanced the ability of cBMSCs and their supernatant to suppress the proliferation of murine spleen lymphocytes. Lymphocyte subtyping evaluation revealed that cBMSCs and their supernatant diminished the percentage of CD3 + CD4 + and CD3 + CD8 + lymphocytes compared with the control group, with a decreasing CD4 + /CD8 + ratio. Notably, exposure to IFN-γ decreased the CD4 + /CD8 + ratio more effectively than unstimulated cells or supernatant. Additionally, IFN-γ-stimulation increased the mRNA levels of the Th1 cytokines TNF-α, and remarkably decreased the mRNA level of the Th2 cytokine IL-4 and IL-10. Conclusion Our findings substantiate that IFN-γ stimulation can enhance the immunomodulatory properties of cBMSCs by promoting TLR3-dependent activation of the IDO/kynurenine pathway, increasing the secretion of immunoregulatory molecules and strengthening interactions with T lymphocytes, which may provide a meaningful strategy for the clinical application of cBMSCs in immune-related diseases.